Recombinant WDR5(S22-C334), WD40 repeat-containing protein 5

Our truncated human WDR5 (S22 - C334) construct enables sufficient expression of soluble and stable protein in E. coli.

Protein Construct: S22-C334
Source: Human
Expression Host: Escherichia coli
Molecular weight [kDa]: 34.35
pI: 8.64
Extinction Coefficient [M^-1cm^-1]: 68410
Concentration [mg/mL]: 10.57
Storage Buffer: 20 mM HEPES pH 7.0, 250 mM NaCl, 5 mM DTT
Tag: none

Amino acid sequence:

QC Data: Datasheet
Purity SDS: >95 %
Hydrodynamic Radius (nm): 2.49
Polydispersity Index (PDI): 0.03
T_on (°C): 53.7
T_m (°C): 65.4
Calculated Mass [Da]: 34325.368
Measured Mass [Da]: 34323.39

WDR5 Structure drives function diversity

WDR5 is well known for acting as a scaffold protein that enables the assembly of numerous complexes. Its highly conserved β-propeller structure gives WDR5 its toroidal shape, which is essential for its function, as it features the "WDR5-binding" (WBM) motif on one side and the "WDR5-interacting (WIN) motif on the other surface. These sites enable the engagement of WDR5 in nearly 200 different protein interactions.

Key functions

WDR5 plays an important role in chromatin modification: It is able to catalyze H3K4 methylation via complex formation with MLL/SET1, which is typically associated with gene activation or enforce gene silencing by complexation with NuRd. These versatile functions make WDR5 a key player in epigenetic regulation across different tissues and cellular contexts.
One main regulatory process involving WDR5 is maintenance of muscle homeostasis: Skeletal muscle regeneration relies on muscle-specific stem cells, or satellite cells, which express the transcription factor PAX7 to drive adult myogenesis. PAX7 recruits WDR5 and the MLL complex to regulatory regions of Myf5, promoting chromatin accessibility, H3K4me3 enrichment, and Myf5 expression. This highlights H3K4 methylation as a key aspect of WDR5 function, as loss of WDR5 significantly reduces H3K4me levels at specific muscle gene promoters.

Oncogenic Role

In cancers driven by MLL fusion proteins (a common cause of aggressive leukemia), WDR5 is co-opted to drive aberrant H3K4 methylation and constitutive activation of pro-leukemic genes. Its dual degradation together with the Ikaros zinc finger (IKZF) transcription factor is a promising anti-cancer strategy.

Targeting Strategy

Small molecule inhibitors that successfully compete with the H3 peptide for binding in the central pocket of WDR5 are powerful tools for disrupting the complex's ability to methylate H3K4, offering a promising therapeutic approach for MLL-rearranged leukemias.